Hum. Reprod. Advance Access published online on September 3, 2009
Human Reproduction, doi:10.1093/humrep/dep308
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Human decidual stromal cells suppress cytokine secretion by allogenic CD4+ T cells via PD-1 ligand interactions
Department of Obstetrics, Gynecology and Women's Health, University of Missouri-Columbia, One Hospital Drive, 402 Keene St., Columbia, MO 65201, USA
1 Correspondence address. Tel: +1-573-817-3114; E-mail: schustd{at}missouri.edu
BACKGROUND: Although previous reports suggest an antigen-presenting function for decidual stromal cells (DSCs), the relevance of cell-to-cell communication between DSCs and T cells at the human feto-maternal interface has not been fully elucidated. Therefore, we investigated the presence and function of human DSC-expressed B7-H1 and B7-DC co-stimulatory ligands. B7-H1 and B7-DC on peripheral antigen-presenting cells (APC) typically inhibit T cell activation after binding to their corresponding receptor, programmed death-1 (PD-1).
METHODS: DSCs were isolated from human term decidua. The expression of B7-H1/B7-DC and HLA-DR and their alteration following IFN-
and/or TNF-
stimulation were assessed. DSCs with or without IFN- pretreatment were co-cultured with allogenic CD4+ T cells. The effect of PD-1:B7-H1/B7-DC and T cell receptor (TCR):HLA-DR interactions on T cell cytokine production was evaluated by adding blocking antibodies.
RESULTS: DSCs constitutively expressed B7-H1 and B7-DC, as well as small amounts of HLA-DR. Exogenous IFN- and TNF- up-regulated the B7-H1/-DC expression on DSCs, whereas HLA-DR expression was increased only by IFN-. IFN- pretreatment of DSCs stimulated T cell cytokine production through HLA-DR up-regulation. B7-H1 blockade on DSCs strongly enhanced T cell cytokine production (IFN-, TNF- and IL-2), whereas B7-DC blockade had similar but more modest effects. Blockade of both B7-H1 and B7-DC resulted in additive effects.
CONCLUSIONS: Our findings support the categorization of human DSCs as non-professional APCs and suggest that PD-1 ligands on DSCs, together with major histocompatibility complex class II, may play a crucial role in the regulation of decidual CD4+ T cell cytokine production. This helps to maintain a balanced cytokine milieu at the feto-maternal interface.
Key words: cell culture/cell signaling/immunology
These authors contributed equally to this work. Submitted on April 9, 2009; resubmitted on July 13, 2009; accepted on August 7, 2009.